Alopecia in Epidermolysis Bullosa

Hair abnormalities observed in epidermolysis bullosa (EB) are of variable severity and include mild hair shaft abnormalities, patchy cicatricial alopecia, cicatricial alopecia with a male pattern distribution, and alopecia universalis. Alopecia is usually secondary to blistering, and scalp areas more exposed to friction, such as the occipital area, are involved more frequently. This article reviews the hair abnormalities reported in the different subtypes of EB.

The expression of the basement membrane zone (BMZ) components in the anagen hair follicles of the human scalp is similar to that of interfollicular epidermis, with expression of plectin, 180-kD bullous pemphigoid antigen (BP180), 230-kD bullous pemphigoid antigen (PB230), α6β4 integrin, laminin 311, laminin 332, and type 4 and type 7 collagen. Expression of the BMZ components, however, varies according with the different follicular portions. In particular, the upper and middle portions of the hair follicle (infundibulum and isthmus), including the bulge region, show expression of all BMZ components with a labeling intensity under immunofluorescence similar to that found in the interfollicular epidermis. In the lower part of the follicle and in the hair bulb, expression of laminin 311 and collagen 4 is continuous, but labeling for other BMZ components shows a gradual decrease with discontinuous expression of α6β4 integrin and laminin 332, particularly outside the hair bulb. Between the dermal papilla and the epithelial cells inside the hair bulb, all of the BMZ components are evident, with the exception of the BP230. The reduced expression of all BMZ components outside the hair bulb and the complete absence of BP230 at the dermal papilla junction seem to be responsible for the incomplete ultrastructure of hemidesmosomes in these regions. Desmosomes are also important in hair structure and function. These components include the desmogleins 1 and 3 (involved in pemphigus foliaceus and vulgaris, respectively, where alopecia can result from an autoimmune mechanism), desmoplakins, plakophilin, and plakoglobin.

Taken together, these findings show that in normal conditions the BMZ components are expressed to a lesser degree in the transient regions of the hair follicles as compared with the permanent region (the upper portion of the follicle). The complete structure of the hemidesmosomes is then responsible for the stabilization of the upper follicle to the surrounding connective tissues, while the incomplete hemidesmosome structure may facilitate the movement of the transient region.

Blistering of the scalp involving the lamina lucida and below, as in junctional and dystrophic forms of epidermolysis bullosa (EB), usually leads to cicatricial alopecia secondary to the inflammatory process in the interfollicular epidermis and in the upper portion of the hair follicle. As the BMZ components are similar at these sites, absence or anomalous formation of the specifically affected proteins increases hair and skin fragility secondary to trauma. In this way, blister formation in the occipital area is very common, as it is an important support area of the scalp. The occurrence of alopecia in different forms of EB is summarized in Table 1 .

Table 1

Classification of EB and hair abnormalities in the different subtypes of EB

Subtypes

Hair/Scalp Involvement

EB simplex

EBS superficialis AD

None

Lethal acantholytic EBS AR

Alopecia universalis

Plakophilin deficiency AR

Sparse, dry, wiry hair; loss of eyelashes/eyebrows

EBS localized AD

None

Dowling-Meara AD

None

EBS other generalized AD (previously called Koebner)

None

Autosomal recessive EBS

None

EBS-Ogna AD

None

EBS migratory circinate

None

EBS with mottled pigmentation

None

EBS with muscular dystrophy

Occasional congenital alopecia

EBS with pyloric atresia

None

JEB (junctional EB)

Herlitz AR

May occur, particularly if there is survival long term to develop cicatricial alopecia